The abnormal pattern of visual evoked potentials in rabbits with hepatic encephalopathy (HE) due to fulminant hepatic failure (FHF) resembles that induced by barbiturates and benzodiazepines. As these drugs induce neural inhibition by interacting with receptors for the inhibitory neurotransmitter Gamma-aminobutyric acid (GABA) on postsynmaptic neural membranes, this finding implies that neuronal activity in HE is similar to that induced by GABA. Outside the CNS the main source of GABA is gut bacteria and the main site of its catabolism is the liver. When FHF was induced in rabbits the onset of HE was preceded by a marked increase in plasma GABA levels and by an increase in the permeability of the blood brain barrier (BBB). FHF was associated with a twofold increase in the number of GABA receptors on postsynaptic membranes. These findings suggest that as the liver fails: 1) impaired hepatic metabolism of GABA leads to an increase of gut-derived GABA in plasma, 2) plasma GABA gains access to the brain through a permeable BBB and induces neural inhibition and 3) up-regulation of GABA receptors may increase the sensitivity of the brain to GABA. The status of receptors for other neurotransmitters and the composition of synaptic plasma membranes in HE are currently being studied.